Myoclonus-dystonia: clinical and electrophysiologic pattern related to SGCE mutations.

OBJECTIVE: To clarify the clinical and neurophysiologic spectrum of myoclonus-dystonia patients with mutations of the SGCE gene. METHODS: We prospectively studied 41 consecutive patients from 22 families with documented mutations of the SGCE gene. The patients had a standardized interview, neurologic examination, and detailed neurophysiologic examination, including surface polymyography, long-loop C-reflex studies, and EEG jerk-locked back averaging. RESULTS: We noted a homogeneous electrophysiologic pattern of myoclonus of subcortical origin with short jerks (mean 95 msec, range 25 to 256 msec) at rest, during action, and during posture; there were no features of cortical hyperexcitability (specifically no abnormal C-reflex response and no short-latency premyoclonic potential on back-averaging studies). Myoclonus was either isolated or associated with mild to moderate dystonia, and predominated in the neck/trunk or proximal upper limbs in most cases. We found that 22% of the patients had a spontaneous improvement in their dystonia before reaching adulthood and that hypotonia can occasionally be a presenting symptom of the disorder. CONCLUSION: We describe the myoclonus in patients with mutations in the SGCE gene and characterize the electrophysiologic pattern of this myoclonus. This pattern may help to improve the sensitivity of molecular tests and to define homogeneous populations suitable for inclusion in therapeutic trials.

[Human herpes virus type 6, etiology of an acute encephalitis in childhood: case report]. / L'HHV-6, une cause de leucoencéphalite aiguë disséminée du nourrisson: à propos de 1 observation.

Primary infection with human herpesvirus-6 (HHV-6) causes the classical roseola infantum. Otherwise the infection is clinically silent but it may sometimes be responsible for central nervous system involvement. In order to illustrate such a type of lesions, we report on a 16-month-old girl with acute leucoencephalitis. The disease started with pyrexia 40 degrees C, followed by an episode of seizure, erythematous rash on the trunk and then coma. Brain MRI showed wide lesions on white matter. HHV-6 DNA was detected by PCR in the CSF and serum at the acute stage, and tests for HHV-6 antibody showed a significant increase of IgG antibody titre between acute and convalescent sera. One month later complete clinical recovery was observed while the MRI showed a partial disappearance of the lesions. The sero-conversion associated with the detection of the viral DNA in the serum identified a primary HHV-6 infection and the detection of viral nucleic acid in CSF gives arguments for the responsibility of the virus in the pathogenesis. When facing an acute leuco-encephalitis in infants, it is important to perform exhaustive virology investigations to rule out the implication of HHV-6 as well as other commonly incriminated pathogens (EBV, CMV, mycoplasma, enterovirus) to avoid accusing wrongly the vaccines.

Epsilon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes.

BACKGROUND: Myoclonus dystonia syndrome (MDS) is an autosomal dominant movement disorder caused by mutations in the epsilon-sarcoglycan gene (SGCE) on chromosome 7q21. METHODS: We have screened for SGCE mutations in index cases from 76 French patients with myoclonic syndromes, including myoclonus dystonia (M-D), essential myoclonus (E-M), primary myoclonic dystonia, generalised dystonia, dystonia with tremor, and benign hereditary chorea. All coding exons of the SGCE gene were analysed. The DYT1 mutation was also tested. RESULTS: Sixteen index cases had SGCE mutations while one case with primary myoclonic dystonia carried the DYT1 mutation. Thirteen different mutations were found: three nonsense mutations, three missense mutations, three splice site mutations, three deletions, and one insertion. Eleven of the SGCE index cases had M-D and five E-M. No SGCE mutations were detected in patients with other phenotypes. The total number of mutation carriers in the families was 38, six of whom were asymptomatic. Penetrance was complete in paternal transmissions and null in maternal transmissions. MDS patients with SGCE mutation had a significantly earlier onset than the non-carriers. None of the patients had severe psychiatric disorders. CONCLUSION: This large cohort of index patients shows that SGCE mutations are primarily found in patients with M-D and to a lesser extent E-M, but are present in only 30% of these patients combined (M-D and E-M).

Demyelinating peripheral neuropathy associated with hemophagocytic lymphohistiocytosis. An immuno-electron microscopic study.

We report the case of an 11-year-old male who developed subacute diffuse polyradiculoneuropathy, associated with digestive symptoms and Epstein-Barr virus infection. Parental consanguinity was present. The laboratory findings including bone marrow smear were consistent with hemophagocytic lymphohistiocytosis (HLH). Electrophysiological study of peripheral nerves revealed an intense and diffuse demyelinating process. The histological nerve lesions were severe and purely demyelinating. Most axons were intact. There was a diffuse infiltration of the nerve parenchyma by mononuclear cells. Immuno-electron microscopic study evidenced entry of macrophages into Schwann cell cytoplasm with dissociation of myelin sheaths. This boy died several months after the onset of the neuropathic symptoms. HLH is a rare genetic or acquired disorder in childhood characterized by abnormal immune activation, which induces an uncontrolled inflammatory response with sustained hyperactivation of T lymphocytes and macrophages. Only very rare cases of peripheral nerve involvement have been described in HLH. This is the first case showing that peripheral nerves, as other viscera, may be destroyed by the macrophagic infiltration, which characterizes HLH.

[Parent's information and prenatal diagnosis of cerebral malformation with an uncertain prognosis]. / Information des couples et diagnostic prénatal d'une malformation cérébrale à pronostic incertain: analyse des pratiques.

UNLABELLED: Fetal ultrasounds examinations allow identification of brain malformations; announce of diagnosis and information about prognosis may be difficult when malformation is rare and prognosis uncertain. OBJECTIVES: In this study we tried to analyze how fetal imaging for prenatal screening was organized and how couples were managed and supported. METHODS: We focused on the procedures used to inform couples: content, method of delivery and consequences. A referent physician in each large multidisciplinary center for prenatal diagnosis in Paris area was questioned by semi-directed interview. RESULTS: Our study showed that it is difficult to standardize the way in which information is supplied before and after fetal ultrasounds examination; uncertainty about prognosis led more often to abortion. CONCLUSION: Thus, couples should have clear and complete information provided by a multidisciplinary team including specialists particularly concerned by the malformation (neuropediatrician and/or neurosurgeon)--moreover when prognosis is uncertain, in order to support them, and to accompany their decision concerning pregnancy.

Infantile spasms with basal ganglia MRI hypersignal may reveal mitochondrial disorder due to T8993G MT DNA mutation.

PURPOSE: To report three cases of infantile spasms (IS) with an abnormal magnetic resonance imaging signal in the basal ganglia (Leigh-like syndrome), due to T8993G mt DNA mutation. PATIENTS AND RESULTS: The first sign was, at the end of the first year of life, IS in one case and the combination of IS with behavior changes in the two other cases. Video EEG polygraphy demonstrated both spasms and hypsarrhythmia, but no other kind of seizures. Vigabatrin or steroids controlled the spasms with a follow-up of several years. All 3 patients had hyperlactatorrhachia (3.47 to 7 mmol/l). Axial hypotonia and dystonia appeared by the end of the first year of life. As in cases with the NARP mutation and onset later in life, neuropathy and retinopathy could also be demonstrated. DISCUSSION: Although it is well established that symptomatic IS with hypsarrhythmia mainly result from cortical lesions, this epileptic encephalopathy may also be generated by lesions in the basal ganglia without evidence of cortical damage. This finding suggests that West syndrome is likely to be caused by age-related dysfunction at any level of a cortico-putaminal loop of hyperexcitability.

Herpes simplex encephalitis relapses in children: differentiation of two neurologic entities.

Relapses of herpes simplex encephalitis (HSE) occurring after the completion of antiviral treatment have been reported repeatedly in children. The authors report data on six children who had at least one relapse of HSE. Two different mechanisms may account for these relapses, including viral replication or an immuno-inflammatory process, with different therapeutic attitudes. Relapses with viral replication may reveal host susceptibility to herpes simplex virus infection.

Neurological presentation in pediatric patients with congenital disorders of glycosylation type Ia.

OBJECTIVE: Congenital disorders of glycosylation (CDG), formerly called carbohydrate-deficient glycoprotein syndromes, constitute a newly identified group of multisystem disorders characterized by defective glycosylation of N-glycosylated proteins. The objective of this work was to describe precisely neurological findings in patients with type Ia CDG (CDG-Ia) and to compare our results with the literature. STUDY DESIGN: We retrospectively reviewed neurological and neurodevelopmental, neuroimaging, and genetic features in ten patients with CDG-Ia who mainly presented with neurological abnormalities during childhood and therefore were referred to a neuropediatrician or a neurogeneticist. RESULTS: Neurological manifestations had a static clinical course, dominated by mental retardation and cerebellar dysfunction, and acute episodes: stroke-like episodes and seizures. However, microcephaly, retinopathy, and polyneuropathy were progressive. All patients had severe global neurodevelopmental delay: only one was able to walk alone at ten years of age and only one could read. Marked heterogeneity in manifestations and delay of diagnosis was noted across the patients. Cerebellar hypoplasia was found by magnetic resonance imaging in all ten patients and olivopontocerebellar hypoplasia in four patients. As in the literature, there was no clear phenotype-mutation correlation. CONCLUSION: Our findings confirm the importance of a precise and complete description of the neurological and neuroradiological phenotype delineating the phenotype of CDG-Ia to increase the likelihood of diagnosing the disease.

[Efficacy and safety of inhalation premixed nitrous oxide and oxygen for the management of procedural diagnostic pain in neuropediatrics]. / Efficacité et sécurité de l'inhalation de MEOPA pour la pratique d'actes invasifs à visée diagnostique en neuropédiatrie.

AIM: We studied the use of premixed nitrous oxide and oxygen in 80 patients with neurologic diseases. PATIENTS AND METHODS: Mean ages ranged 10 +/- 5 yrs. Twenty-three patients (29%) were mentally retardated among which 17 of them presented with severe epilepsy. Painful procedures consisted of: lumbar punctures (80%), intravenous access (7), gastric endoscopy (6), skin biopsy (4), gastrostomy tube management (3). High-risk children were continuously monitored using ECG, non invasive blood pressure and transcutaneous oxygen saturation. We studied acceptation of the inhalation, vital signs, satisfaction of children, parents, medical and nursing staffs; side effects were compared with a group of healthy children undergoing venous access before induction of anesthesia. RESULTS AND DISCUSSION: Acceptation increased with age. No significant changes in vital signs variables were observed. Satisfaction rate regarding the method was 88% for all children, parents, physicians and nurses. No serious undesirable event (as respiratory depression, seizure, inhalation of gastric content) occurred in these patients. The more frequent side-effects were: drowsiness during and after inhalation (35 and 9% respectively in the handicapped patients); nausea and vomiting (8%), headaches (3%), were more frequent than reported in literature but there were 25% of meningitis among our patients. CONCLUSION: Premixed nitrous oxide and oxygen was effective for reducing procedural pain and anxiety in children with neurological disorders, even in severely handicapped patients, with minor side-effects.

[Optic pathway gliomas in neurofibromatosis type I. Longitudinal study of 30 cases in two multidisciplinary practices]. / Les gliomes des voies optiques dans la neurofibromatose de type 1. Etude longitudinale de 30 cas suivis dans deux consultations multidisciplinaires.

UNLABELLED: The aim of this study was to analyse the outcome of optic pathway gliomas in 30 children with neurofibromatosis type 1, the indications of treatment, and the follow-up and screening protocol. PATIENTS AND METHODS: All patients with a minimal two years follow-up (median six years, range two to 19 years), in two multidisciplinary consultations of Saint-Vincent-de-Paul (Paris) and Purpan (Toulouse) hospitals, were included in the study. In our series, we practiced systematic screening MRI in children under six years' of age or with neuropsychological deficiency that may imply an unreliable ophthalmological examination. RESULTS: Thirty-seven percent (11 patients) had progressive ophthalmological signs and were treated, and 63% (19 patients) were not progressive. Our study confirmed that most of optic pathway gliomas were stable during evolution, but rare cases may have bad prognosis. CONCLUSION: Our study supported the importance of close ophthalmological follow-up during childhood for which screening methods are discussed. There is a consensus to limit treatment for patients with progressive ophthalmological symptoms.

Interferon-beta treatment in patients with childhood-onset multiple sclerosis.

We present a report of the use of interferon-beta before 18 years of age in 16 patients with childhood-onset multiple sclerosis. This study demonstrated that the treatment is safe and well tolerated.

Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation.

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene have recently been reported in 12 patients affected by neuropathologically proved Alexander disease. We searched for GFAP mutations in a series of patients who had heterogeneous clinical symptoms but were candidates for Alexander disease on the basis of suggestive neuroimaging abnormalities. Missense, heterozygous, de novo GFAP mutations were found in exons 1 or 4 for 14 of the 15 patients analyzed, including patients without macrocephaly. Nine patients carried arginine mutations (four had R79H; four had R239C; and one had R239H) that have been described elsewhere, whereas the other five had one of four novel mutations, of which two affect arginine (2R88C and 1R88S) and two affect nonarginine residues (1L76F and 1N77Y). All mutations were located in the rod domain of GFAP, and there is a correlation between clinical severity and the affected amino acid. These results confirm that GFAP mutations are a reliable molecular marker for the diagnosis of infantile Alexander disease, and they also form a basis for the recommendation of GFAP analysis for prenatal diagnosis to detect potential cases of germinal mosaicism.

[Cerebellar vermis hypoplasia with extracerebral involvement (retina, kidney, liver): difficult to classify syndromes]. / Hypoplasies vermiennes avec atteintes extracérébrales (rétine, rein, foie): des syndromes difficiles à classer.

UNLABELLED: Congenital cerebellar vermis hypoplasias diversely associated with retinopathy, nephropathy and hepatopathy are rare syndromes of uncertain nosology. We report three new cases. CASE REPORTS: Case 1. A 3-month-old boy presented a brief nystagmus. At the age of 2 years, he had facial dysmorphia, hypotonia, ataxia, ocular motor apraxia and neurodevelopmental impairment with cerebellar vermis hypoplasia. The electroretinogram showed asymptomatic retinal involvement. At the age of 6 years, he developed chronic renal failure. The diagnosis of familial juvenile nephronophthisis was made by detection of a large homozygous deletion of the NPH1 region. Case 2. A term newborn boy presented apnea, tachypnea, hypotonia, nystagmus, ptosis, lack of visual contact and hepatomegaly. He had facial dysmorphia, bilateral optic coloboma with chorioretinal dysplasia and cerebellar vermis hypoplasia. There were cysts in the kidneys with increased echogenicity and lack of demarcation between the pyramids and the cortex. The liver was hyperechoic with fibrosis. At the age of 15 months, the child had severe developmental delay. He had bouts of fever. A search for a large homozygous deletion of the NPH1 region was negative. Case 3. A term newborn girl presented difficulty to suck, cyanosis, hypotonia and ptosis. Later, the child had a developmental delay. At the age of 6 years, she developed chronic renal failure (nephronophthisis). At the age of 23 years, she presented divergent strabismus, ataxia, mental retardation, slow ocular pursuit and facial dysmorphia. The neuroimaging showed a cerebellar vermis hypoplasia. A search for a large homozygous deletion of the NPH1 region was negative. CONCLUSION: The diagnosis of cerebellar vermis hypoplasia requires searching for retina, kidney and liver involvement. The large homozygous deletion of the NPH1 region has to be investigated if typical familial juvenile nephronophthisis is associated. Because cerebellar vermis hypoplasia with extracerebral involvements (retina, kidney, liver) is part of many different closely related syndromes, a clear molecular classification is necessary for accurate genetic counselling and an early prenatal diagnosis.